Effect of an orally ingested mugwort and mushroom extract mixture on urine odor from aged mice.

We had previously found that male mice could be trained to discriminate between the urine odor of aged and young adult (adult) mice. We hypothesized that these odors that characterized the older animals might be inhibited by a mixture of extracts (AAM) of mugwort and mushroom, because previous studies have indicated that these extracts could be used to reduce the intensity of unpleasant body odors. The findings of this chemical study strongly suggest that the AAM function helped to modify the aged mouse urine odor so that it more closely resembled the smell of urine from younger mice. Based on the results of the chemical studies, a set of behavioral experiments were therefore conducted. The results of three sets of generalization trials also strongly supported the results of the chemical studies. Together, these results suggest that ingested AAM decreased the intensity of odors associated with aging in mice.

Analysis of the spontaneous scratching behavior by NC/Nga mice: a possible approach to evaluate antipruritics for subjects with atopic dermatitis.

We investigated the spontaneous scratching by NC/Nga mice to design a new method for evaluating the itch of subjects with atopic dermatitis. The numbers of scratchings in various strains of mice were classified based on the duration of the scratching. Prolonged scratching was frequent in skin-lesioned NC/Nga mice, but not in ICR, BALB/c and non-lesioned NC/Nga mice. Pretreatment with dexamethasone or tacrolimus significantly suppressed long-duration scratching in NC/Nga mice but did not suppress short-duration scratching induced by ovalbumin active cutaneous anaphylaxis in BALB/c mice and in ICR mice subcutaneously injected with histamine. In contrast, pretreatment with chlorpheniramine or ketotifen significantly suppressed short-duration scratching induced by ovalbumin active cutaneous anaphylaxis in BALB/c mice and in ICR mice subcutaneously injected with histamine, but not long-duration scratching seen in NC/Nga mice. These findings indicate that the mechanism of spontaneous scratching in NC/Nga mice differs from that induced by several pruritogen injections. This new method shows good correlation with the therapeutic activity of drugs in cases of atopic dermatitis in humans and may serve as a useful model for evaluating antipruritic drugs and for studying mechanisms involved in atopic dermatitis.

Evaluation of antipruritic effects of several agents on scratching behavior by NC/Nga mice.

We investigated the effects of several agents on the established itching model in NC/Nga mice, model of atopic dermatitis-like disease, to elucidate related characteristics. The number of spontaneous scratching behaviors (the duration time is over 1.5 s) by NC/Nga mice with severe skin lesions was measured before and after administration of agents for 24 h. The scratching behavior by NC/Nga mice was significantly suppressed by administration of dexamethasone or tacrolimus, but not by chlorpheniramine maleate or cyproheptadine hydrochloride. These results suggest that this method shows a good correlation with the effectiveness of drugs prescribed for itching in humans with atopic dermatitis, and histamine and serotonin do not play an important role in causing the scratching behavior seen by NC/Nga mice. The scratching behavior was also significantly suppressed by naloxone hydrochloride, dibucaine or capsaicin. These results suggest that the scratching behavior seen in this model is caused by itching signal transmission through neural system. Furthermore, we found that theophylline, pinacidil or limaprost had scratching suppression effects in this model.

[Effects of ethanol extracts of herbal medicines on dermatitis in an atopic dermatitis mouse model].

Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is characterized by highly pruritic, eczematous skin lesions. Our previous study elucidated that nerve growth factor (NGF) plays an important role in the pathogenesis of skin lesions and inhibition of the physiological effects of NGF can moderate skin lesions in atopic dermatitis. In this study, we investigated the effects of ethanol extracts of herbal medicines on neuritic outgrowth induced by NGF. Four herbal extracts (Geranium thunbergii, Humulus lupulus, Rosmarinus officinalis and Salvia officinalis L.) inhibited NGF-induced neuritic outgrowth in PC12 cells. We also investigated the effects of each herbal extract on dermatitis in NC/Nga, an atopic dermatitis mouse model. The skin lesions of the NC/Nga mice were significantly inhibited by repeated applications of each herbal extract. These results suggested that the four herbal extracts can prevent and moderate the symptoms of atopic dermatitis, and these effects might be appeared by inhibiting the effect of NGF on neuritic outgrowth in lesional skin.

Function and regulation of taurine transport at the inner blood-retinal barrier.

In the retina, taurine exerts a number of neuroprotective functions as an osmolyte and antioxidant. The purpose of the present study was to elucidate the taurine transport system(s) at the inner blood-retinal barrier (BRB). [(3)H]Taurine transport at the inner BRB was characterized using in vivo integration plot analysis and a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells). The expression of the taurine transporter (TauT) was demonstrated by RT-PCR and immunoblot analyses. The apparent influx permeability clearance of [(3)H]taurine in the rat retina was found to be 259 muL/(ming retina), supporting carrier-mediated influx transport of taurine at the BRB. [(3)H]Taurine uptake by TR-iBRB2 cells was Na(+)-, Cl(-)- and concentration-dependent with a K(m) of 22.2 muM and inhibited by TauT inhibitors, such as beta-alanine and hypotaurine. RT-PCR and immunoblot analyses demonstrated that TauT is expressed in TR-iBRB2 and primary cultured human retinal endothelial cells. The uptake of [(3)H]taurine and the expression of TauT mRNA in TR-iBRB2 cells increased under hypertonic conditions but decreased following pretreatment with excess taurine. In conclusion, TauT most likely mediates taurine transport and regulate taurine transport at the inner BRB.

Effects of anti-nerve growth factor antibody on symptoms in the NC/Nga mouse, an atopic dermatitis model.

Nerve growth factor (NGF) is an important substance in the skin, where it can modulate nerve maintenance and repair. However, the direct link between NGF and pruritic disease such as atopic dermatitis is not yet fully understood. To determine whether NGF plays a major role in atopic dermatitis and in the development or maintenance of skin lesions, we performed a study using NC/Nga mice and compared mice with and without skin lesions. Our examinations of the NC/Nga mice sought to detect nerve fibers in the epidermis, measured serum and skin NGF content, and observed skin NGF by immunohistochemistry staining. We also examined the effects of anti-NGF antibody on dermatitis symptoms in NC/Nga mice. In these mice, nerve fibers were significantly increased in the epidermis of lesioned skin, and the NGF content of the serum and skin was significantly elevated. Anti-NGF antibodies significantly inhibited the development and proliferation of skin lesions and epidermal innervation and significantly inhibited any growth in scratching but did not ameliorate scratching already developed. Our findings suggest that NGF plays important roles in the pathogenesis of atopic dermatitis-like skin lesions and that inhibiting the physiological effects of NGF or suppressing increased NGF production may prevent or even moderate the symptoms of atopic dermatitis.